Beckwith-Wiedemann syndrome (BWS); Russell-Silver syndrome (RSS) MLPA
Definition
This entry is grouped in the catalog under the heading "15q11"; this is incorrect, the actual locus is 11p15.5 (15q11-q13 is a separate region belonging to Angelman/Prader-Willi syndromes). Beckwith-Wiedemann syndrome (BWS) is a variable overgrowth syndrome presenting with macroglossia, hemihyperplasia, omphalocele, neonatal hypoglycemia and risk of embryonal tumors (Wilms tumor, hepatoblastoma); it results from dysregulation of two imprinting centers (IC1, IC2) at 11p15.5, with IC2 maternal hypomethylation (~50%), IC1 hypermethylation (~5%), and paternal UPD (~20%). Russell-Silver syndrome is characterized by small size for gestational age at birth, relative macrocephaly and postnatal growth failure; ICR1 hypomethylation at the same region is responsible in 35 to 67% of cases and maternal UPD of chromosome 7 in 7 to 10%, meaning that opposite disruptions of the same region produce entirely opposite phenotypes.
Gene/region examined
15q11 - Deletion/Duplication
Method
MLPA analysis
Accepted sample types
EDTA blood, AF, CVS
Inheritance
Most cases arise as a sporadic/de novo epigenetic change or through UPD, and the recurrence risk is generally low; if a parent carries an ICR copy number change, the risk can rise to as much as 50%.